ham-onc Flashcards
what is hereditary spherocytosis
autosomal dominant defect of red blood cell cytoskeleton
the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
red blood cell survival reduced as destroyed by the spleen
How does Hereditary Spherocytosis present?
failure to thrive
jaundice, gallstones
splenomegaly
aplastic crisis precipitated by parvovirus infection
degree of haemolysis variable
MCHC elevated
How is hereditary spherocytosis diagnosed
the British Journal of Haematology (BJH) guidelines state that ‘patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests
if the diagnosis is equivocal the BJH recommend the EMA binding test and the cryohaemolysis test
for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice
How is Hereditary Sperocytosis managed?
Acute haemolytic crisis:
- treatment is generally supportive
- transfusion if necessary
longer term treatment:
- folate replacement
- splenectomy
What is present in hereditary spherocytosis post splenectomy
Howell-Jolly bodies
Howell-Jolly bodies are remnants of the red blood cell (RBC) nucleus which are normally removed by the spleen. Post-splenectomy these Howell-Jolly bodies persist and can be observed on histology.
What type of RBCs are seen in microangiopthic haemolytic aneamia
Schistocytes are sheared RBCs seen in microangiopathic haemolytic anaemia
when are heinze bodies seen ?
Heinz bodies and bite cells are characteristic of glucose-6-phosphate dehydrogenase (G6PD) deficiency
what are Howell-Joly bodies
Howell-Jolly bodies are seen in hyposplenism
what are pencil cells
pencil cells are a feature of iron deficiency anaemia
when are target cells seen
Sickle-cell/thalassaemia
Iron-deficiency anaemia
Hyposplenism
Liver disease
when are ‘tear drop’ poikiolcytes seen?
myelofibrosis
when are spherocytes seen?
Hereditary spherocytosis
Autoimmune hemolytic anaemia
When does yousee Basophilic stippling
Lead poisoning
Thalassaemia
Sideroblastic anaemia
Myelodysplasia
when do you see Schistocytes (‘helmet cells’)
Intravascular haemolysis
Mechanical heart valve
Disseminated intravascular coagulation
When do you see Burr cells
Uraemia
Pyruvate kinase deficiency
when do you see Acanthocytes
Abetalipoproteinemia
what is hereditary angioedema?
AD condition associated with low plasma levels of C1 inhibitor
what investigations would be done for hereditary angioedema?
C1-INH level is low during an attack
low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool
what are the symptoms of hereditary angioedema?
attacks may be proceeded by painful macular rash
painless, non-pruritic swelling of subcutaneous/submucosal tissues
may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema)
urticaria is not usually a feature
how do you manage hereditary angioedema?
acute
- HAE does not respond to adrenaline, antihistamines, or glucocorticoids
- IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available
prophylaxis: anabolic steroid Danazol may help
what is ITP
Immune (or idiopathic) thrombocytopenic purpura (ITP) -
an immune mediated reduction in the platelet count
Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
when does ITP occur in children
usually following infection or vaccination
what are the symptoms of ITP
isolated thrombocytopenia in a well adult - often not symptomatic
symptomatic patients may present with:
petechiae, purpura
bleeding (e.g. epistaxis)
catastrophic bleeding (e.g. intracranial) is not a common presentation
what investigations for ITP
full blood count: isolated thrombocytopenia
blood film
a bone marrow examination is no longer used routinely
antiplatelet antibody testing has poor sensitivity and doesn’t affect clinical management so is not commonly done
what is the management of ITP
first-line treatment for ITP is oral prednisolone
pooled normal human immunoglobulin (IVIG) may also be used
- it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required
splenectomy is now less commonly used
What is Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)
what is tumour lysis syndrome
Tumour lysis syndrome (TLS) is a potentially deadly condition related to the treatment of high-grade lymphomas and leukaemias. It can occur in the absence of chemotherapy but is usually triggered by the introduction of combination chemotherapy. On occasion, it can occur with steroid treatment alone.
when does tumour lysis syndrome occur?
TLS occurs from the breakdown of the tumour cells and the subsequent release of chemicals from the cell.
what would bloods show in tumour lysis syndrome?
It leads to a high potassium and high phosphate level in the presence of a low calcium. It should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level.
how do you prevent tumour lysis syndrome?
IV fluids
patients are higher risk should receive either allopurinol or rasburicase
rasburicase - a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys
generally preferred now for patients at a higher risk of developing TLS
allopurinol - generally used for patients in lower-risk groups
rasburicase and allopurinol should not be given together in the management of tumour lysis syndrome as this reduces the effect of rasburicase
what grading system is used for tumour lysis syndrome?
Cairo-Bishop system
Laboratory tumor lysis syndrome: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy.
uric acid > 475umol/l or 25% increase
potassium > 6 mmol/l or 25% increase
phosphate > 1.125mmol/l or 25% increase
calcium < 1.75mmol/l or 25% decrease
Clinical tumor lysis syndrome: laboratory tumour lysis syndrome plus one or more of the following:
increased serum creatinine (1.5 times upper limit of normal)
cardiac arrhythmia or sudden death
seizure
what is used for the management of vWD
desmopressin
how is VWD inherited?
AD
what is the role of von willer brand factor?
large glycoprotein which forms massive multimers up to 1,000,000 Da in size
promotes platelet adhesion to damaged endothelium
carrier molecule for factor VIII
what are the types of vWD
type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)
what is the investigations for vWD
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
how is vWD managed?
tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate
what are the symptoms of lead poisoning
Basophillic stippling on blood film
abdo pain
constiation
peripheral neuropathy
associated microcytic anaemia
fatigue
how is lead poisoning managed?
Management - various chelating agents are currently used:
dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
what chromosome is found in CML
t(9;22) - Philadelphia chromosome
present in > 95% of patients with CML
this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22
the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
poor prognostic indicator in ALL
what chromosome is seen in acute promyelocytic leukaemia?
t(15;17)
what chromosome is seen in burkitt’s symphoma
t(8;14)
MYC oncogene is translocated to an immunoglobulin gene
what chromosome is seen in mantle cell lymphoma
t(11;14)
deregulation of the cyclin D1 (BCL-1) gene
what chromosome is seen in follicular lymphoma?
t(14;18)
increased BCL-2 transcription
what gene is associated with prostate cancer ?
BRCA 2
what gene is associated with familial adenomatous polyposis?
APC
what is Li-Fraumeni syndrome?
Autosomal dominant
Consists of germline mutations to p53 tumour suppressor gene
High incidence of malignancies particularly sarcomas and leukaemias
Diagnosed when:
*Individual develops sarcoma under 45 years
*First degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age
what is lynch syndrome
Autosomal dominant
Develop colonic cancer and endometrial cancer at young age
80% of affected individuals will get colonic and/ or endometrial cancer
High risk individuals may be identified using the Amsterdam criteria
Amsterdam criteria
Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two.
Two successive affected generations.
One or more colon cancers diagnosed under age 50 years.
Familial adenomatous polyposis (FAP) has been exclude
what is Gardners syndrome
Autosomal dominant familial colorectal polyposis
Multiple colonic polyps
Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts
Desmoid tumours are seen in 15%
Mutation of APC gene located on chromosome 5
Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer
Now considered a variant of familial adenomatous polyposis coli
what is oral allergy syndrome
Oral allergy syndrome, also known as pollen-food allergy, is an IgE-mediated hypersensitivity reaction to specific raw, plant-based foods including fruits, vegetables, nuts and certain spices. It typically presents with mild tingling or pruritus of the lips, tongue and mouth.
what is used to avoid transfusion-associated graft versus host disease?
irradiated blood products
his is particularly important in immunocompromised patients, such as those with lymphoma who have undergone chemotherapy.
what is beta-thalassemia trait?
Beta-thalassaemia trait is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia. It is usually asymptomatic
what are the features of beta thalassaemia trait
mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
HbA2 raised (> 3.5%)
what are the common tumours that cause bone mets?
prostate
breast
lung
what kind of infection is most likely to occur following platelet transfusion?
Platelet transfusions are at particular risk of bacterial contamination as they are stored at room temperature
what will be on the blood tests in microangiopathic haemolytic anaemia?
anaemia, low haptoglobin and schistocytes
what it TTP?
Pathogenesis of thrombotic thrombocytopenic purpura (TTP)
abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns (‘cleaves’) large multimers of von Willebrand’s factor
overlaps with haemolytic uraemic syndrome (HUS
what are the features of TTP
Features
rare, typically adult females
fever
fluctuating neuro signs (microemboli)
microangiopathic haemolytic anaemia
thrombocytopenia
renal failure
what are the causes of TTP
Causes
post-infection e.g. urinary, gastrointestinal
pregnancy
drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
tumours
SLE
HIV
what leads to TTP in pregnancy?
Pregnancy is a secondary cause of this condition, which is caused by acquired inhibition of ADAMTS13. This is a metalloproteinase responsible for breaking large multimers von Willebrand factor (vWF) into smaller sub-units. The increased amount of circulating vWF results in platelet adhesion and thrombosis. Platelets are used up in creating thrombi and paradoxically, the overall amount of circulating platelets is subsequently reduced, resulting in a tendency to bleed.
how does anastrozole and letrozole work?
they are aromatase inhibitors that reduce peripheral oestrogen synthesis
what symptoms do you get in neoplastic spina cord compression?
back pain - may be worse on lying down/coughing
lower limb weakness
sensory changes: sensory loss and numbness
neurological signs depend on the level of the lesion. Lesions above L1 usually result in upper motor neuron signs in the legs and a sensory level. Lesions below L1 usually cause lower motor neuron signs in the legs and perianal numbness. Tendon reflexes tend to be increased below the level of the lesion and absent at the level of the lesion
what is myelofibrosis
a myeloproliferative disorder
thought to be caused by hyperplasia of abnormal megakaryocytes
the resultant release of platelet derived growth factor is thought to stimulate fibroblasts
haematopoiesis develops in the liver and spleen
features of myelofibrosis?
e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
massive splenomegaly
hypermetabolic symptoms: weight loss, night sweats etc
what are the lab findings in myelofibrosis ?
anaemia
high WBC and platelet count early in the disease
‘tear-drop’ poikilocytes on blood film
unobtainable bone marrow biopsy - ‘dry tap’ therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)
what is autoimmune haemolytic anaemia?
Autoimmune haemolytic anaemia (AIHA) may be divided in to ‘warm’ and ‘cold’ types, according to at what temperature the antibodies best cause haemolysis. It is most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs.
Warm is the most common type of AIHA. In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen
The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud’s and acrocynaosis. Patients respond less well to steroids
what are the investigations for autoimmune haemolytic anaemia?
general features of haemolytic anaemia
anaemia
reticulocytosis
low haptoglobin
raised lactate dehydrogenase (LDH) and indirect bilirubin
blood film: spherocytes and reticulocytes
specific features of autoimmune haemolytic anaemia
positive direct antiglobulin test (Coombs’ test).
what are the causes and management of warm autoimmune haemolytic anaemia?
Causes
idiopathic
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia
lymphoma
chronic lymphocytic leukaemia
drugs: e.g. methyldopa
Management
treat underlying disorders
steroid (+/- rituximab)
what are the causes of cold autoimmune haemolytic anaemia?
Causes of cold AIHA
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
what cytotoxic agent is most commonly associated with ototoxicity?
Cisplatin
what cn H.pylori infection lead to?
Helicobacter pylori infection can lead to gastric lymphoma (MALT). These are typically arise in the antrum of the stomach and can present with systemic features such as fevers and night sweats.
what malignancy can EBV lead to
Hodgkin’s and Burkitt’s lymphoma, nasopharyngeal carcinoma
